Reference:
British Society of Gastroenterology guidelines
Diarrhea and colitis
Diagnostic workup for grade 1 diarrhea or colitis symptoms should include CBC, CMP, and fecal lactoferrin.
Additional workup should be performed for patients with diarrhea or colitis symptoms of grade ≥2, and these additional tests should include fecal calprotectin, and stool infectious analysis (stool ova and parasite, C. difficile and cytomegalovirus (CMV) testing via polymerase chain reaction (PCR) if available or if high index of suspicion is present, among other infectious studies (eg, COVID-19)). Serum TSH and celiac serologies (antitransglutaminase antibodies with total IgA level) may also be considered, if clinical suspicion of ICI-induced celiac disease is present. Stool: lactoferrin and calprotectin; blood: ESR and CRP
Fecal pancreatic elastase if steatorrhea or failure to respond to front line steroids in 24-48 hr
Abdominal CT scan should be obtained in patients with signs and symptoms of colitis complications, such as bowel perforation or toxic megacolon. Flexible sigmoidoscopy and/or colonoscopy with biopsy should be performed for patients with diarrhea or colitis symptoms of grade ≥3 or with persistent (≥5 days) diarrhea or colitis symptoms of grade 2 . Contraindicated if acute abdomen such as toxic megacolon or perforation or if ANC < 1.0
ICIs may be temporarily withheld (instead of discontinued) in patients experiencing grade ≥3 diarrhea or colitis symptoms. These patients may be re-challenged with ICIs if their symptoms are stable (grade ≤1 or baseline) with <10 mg/day of prednisone (or equivalent)
Prior to administration of infliximab or vedolizumab, patients should be tested for HBV, HIV, and TB. Administration of infliximab or vedolizumab should not be delayed if test results are pending.
if there is severe ulcerative presentation on colonoscopy, 3 doses of infliximab (5 mg/kg) should be administered at 0, 2, and 6 weeks to reduce the risk of colitis recurrence
If diarrhea or colitis symptoms persist after the second dose of infliximab treatment, the third dose should be held and 3 doses of vedolizumab (300 mg) should be administered at 0, 2, and 6 weeks.
If no clinical improvement is observed following immunosuppressive therapy in patients with grade ≥3 diarrhea or colitis, a repeat endoscopy with infectious workup (C. difficile and CMV) should be performed. Repeat endoscopy should be performed prior to resuming ICI therapy.
If diarrhea or colitis symptoms recur following corticosteroid taper, they should be evaluated and treated in the same manner as the first episode
Flexible sigmoidoscopy or colonoscopy on admission to the hospital if no evidence of acute abdomen:
An infectious cause for the diarrhea should be excluded in all patients. Patients with grade 1 symptoms are managed conservatively. Patients with grade 2 or higher symptoms should undergo a colonoscopy and are treated with systemic corticosteroids and, depending on their response, biologic therapy.
Perform colonoscopy and EGD only if ANC > 0.5 K/microliter
Examine biopsies for the presence of CMV and other opportunistic infections in immunosuppressed patients
Order EGD if there are signs and symptoms of concurrent nausea/vomiting and/or epigastric pain
Esophageal biopsies are strongly recommended if there is visible evidence of esophageal inflammation on endoscopy
Although the British Society of Gastroenterology (BSG) recommends performing a colonoscopy on all patients with GI irAEs, the AGA reserves endoscopic evaluation for patients with grade 2 or higher GI irAEs.
Endoscopy should be considered before initiation of high-dose systemic glucocorticoids, in patients with corticosteroid-refractory disease, and in those previously exposed to immunosuppressants to exclude the presence of opportunistic infections.
Because 98% of GI irAEs involve the left colon, a flexible sigmoidoscopy rather than a full ileocolonoscopy can be performed in most cases.
The presence of deep, large ulcers is a high-risk feature and associated with increased need for biologic therapy, increased need for hospitalization, and longer hospital stays. Colonic ulcers are the only identifiable predictor of response to treatment and need for biologic therapy.
In some situations, follow-up endoscopy is important to monitor response to therapy and determine the appropriate time to resume ICIs. Alternatively, recent evidence has demonstrated that fecal calprotectin is strongly associated with endoscopic severity in patients with immune-mediated colitis and may serve as a useful noninvasive marker of endoscopic and histologic remission. Fecal calprotectin > 116.
General guidelines
Patients should receive dedicated education on irAEs by a medical professional and may receive additional materials such as informational booklets or reference cards.
Patients should be encouraged to use contraception while receiving immunotherapy. Fertility should be discussed prior to treatment. Per NCCN use contraception for 6 months after the last dose.
When beginning corticosteroid therapy, patients should be specifically counseled about potential toxicities, including hyperglycemia, mood disturbances, insomnia, gastritis, weight gain, and opportunistic infections (eg, Pneumocystis pneumonia)
The following tests should be performed prior to beginning ICI therapy: complete blood count (CBC) with differential, comprehensive metabolic panel (CMP), thyroid-stimulating hormone (TSH), free thyroxine (fT4). Urinalysis should be considered to evaluate for baseline kidney disease.
Consider performing a baseline electrocardiogram (EKG) on patients deemed at a higher risk for myocarditis (eg, cardiac comorbidities, diabetes mellitus, anti-PD-(L)1 with anti-CTLA-4 ICI combination therapy, etc). Baseline troponin testing may also be considered to provide information for evaluating potential future cardiac toxicity.
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